scholarly journals Adult Height in Girls with Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues and Growth Hormone

1999 ◽  
Vol 84 (2) ◽  
pp. 449-452 ◽  
Author(s):  
Anna Maria Pasquino ◽  
Ida Pucarelli ◽  
Maria Segni ◽  
Marco Matrunola ◽  
Fabio Cerrone
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Final Height ◽  
Pubertal Development ◽  
Central Precocious Puberty ◽  
Chronological Age ◽  
Control Group ◽  
Bone Maturation ◽  
Gnrh Analogues ◽  
Age Progression

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 μg/kg im every 21 days, for at least 2–3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg·week sc, 6 days weekly, for 2–4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean ± sem): 13.2 ± 0.2 in GnRHa plus GH vs. 13.0 ± 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 ± 1.3 vs. 152.7 ± 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 ± 2.5 vs. 155.5 ± 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 ± 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 ± 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2–3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.

Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls

2019 ◽  
Vol 105 (3) ◽  
pp. 705-715 ◽  
Author(s):  
Junfen Fu ◽  
Jianwei Zhang ◽  
Ruimin Chen ◽  
Xiaoyu Ma ◽  
Chunlin Wang ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Critical Parameters ◽  
Control Group ◽  
Target Height ◽  
Height Gain ◽  
Chinese Girls ◽  
Rhgh Treatment

Abstract Context Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. Objective To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. Design and Setting Retrospective, multicenter observational study from 1998 to 2017. Participants Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n = 118), GnRHa alone (n = 276), or no treatment (n = 54). Main Outcome Measures FAH, target height (Tht), and predictive adult height (PAH). Results The height gain (FAH–PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (P < 0.05; 9.51 ± 0.53, 8.07 ± 0.37, and 6.44 ± 0.91 cm, respectively). The genetic height gain (FAH–Tht) was 4.0 ± 0.5 cm for the GnRHa + rhGH group and 2.0 ± 0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, 5 critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH–PAH), and this was further validated using an independent study. Conclusions The overall beneficial effect of GnRHa + rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

scholarly journals Increased Final Height in Precocious Puberty after Long-Term Treatment with LHRH Agonists: The National Institutes of Health Experience

2001 ◽  
Vol 86 (10) ◽  
pp. 4711-4716 ◽  
Author(s):  
Karen Oerter Klein ◽  
Kevin M. Barnes ◽  
Janet V. Jones ◽  
Penelope P. Feuillan ◽  
Gordon B. Cutler Jr.
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Final Height ◽  
Bone Age ◽  
Chronological Age ◽  
Lhrh Agonist ◽  
Duration Of Treatment ◽  
Long Term Treatment ◽  
Predicted Height

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3± 2.1 yr old at the start of treatment and were treated with either deslorelin (4 μg/kg·d sc) or histrelin (4–10 μg/kg·d) for an average of 6.1 ± 2.5 yr. Final height averaged 159.8 ± 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 ± 9.6 cm) but still significantly less than midparental height (MPH) (163.7 ± 5.6). Final height averaged 171.1 ± 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 ± 14.2 cm) but still significantly less than MPH (178.3 ± 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height sd score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

scholarly journals Precocious puberty: a clinical review

2018 ◽  
Vol 7 (3) ◽  
pp. 771
Author(s):  
Pallavee P. ◽  
Rupal Samal
Keyword(s):  
Precocious Puberty ◽  
Pubertal Development ◽  
Psychosocial Problems ◽  
Central Precocious Puberty ◽  
Biochemical Tests ◽  
Gnrh Analogues ◽  
Premature Thelarche ◽  
Epiphyseal Fusion ◽  
Peripheral Precocious Puberty

Precocious puberty is defined as pubertal development occurring more than 2.5 standard deviations earlier than the average age. It may comprise of central or gonadotropin-dependent precocious puberty and peripheral or gonadotropin-independent precocious puberty. Variants of precocious puberty include premature thelarche, premature pubarche and isolated premature menarche which principally implies onset of menstruation without any other signs of sexual development. Precocious puberty may have long-term consequences including short stature later on in adulthood owing to premature epiphyseal fusion as also psychosocial problems. Evaluation includes a detailed history, physical examination, biochemical tests and imaging directed towards detecting the cause. Gonadotropin Releasing Hormone (GnRH) analogues are effective for treatment of central precocious puberty. Treatment of peripheral precocious puberty should be based on the cause. Isolated variants are usually normal but should be closely monitored. Multi-speciality consultation with involvement of pediatricians and enocrinologists may improve treatment outcomes in these children, who otherwise pose significant challenges to the gynaecologist.

Treatment of central precocious puberty and early puberty with GnRH analog in girls with Williams-Beuren syndrome

2015 ◽  
Vol 28 (11-12) ◽  
Author(s):  
Sarah Spielmann ◽  
Carl Joachim Partsch ◽  
Angela Gosch ◽  
Rainer Pankau
Keyword(s):  
Adult Female ◽  
Precocious Puberty ◽  
Final Height ◽  
Central Precocious Puberty ◽  
Control Group ◽  
Age At Menarche ◽  
Early Puberty ◽  
Gnrh Analog ◽  
Female Patients ◽  
Significant Difference

AbstractLittle has been published on treatment of precocious puberty in girls with Williams-Beuren syndrome (WBS), a condition occurring frequently in this group. We analyzed our own data on growth/age at menarche of now adult female patients with WBS being diagnosed with central precocious puberty or early puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH) analog (n=13) were compared with those not treated (control group, n=11).Longitudinal data on the somatic development of 24 now adult female patients were analyzed.Medium final height was 157.2±6.5 cm compared to 151.4±5.6 cm in the control group. No significant difference could be found in the discrepancy of genetic target height and final height. Prepubertally girls were normal weight in both groups; in adulthood the majority of patients were overweight/obese. Menarche commenced 11 months after cessation of therapy.As already known from other studies, hormonal suppression via GnRH analog was well tolerated.

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty

2016 ◽  
Vol 174 (3) ◽  
pp. R79-R87 ◽  
Author(s):  
Federica Guaraldi ◽  
Guglielmo Beccuti ◽  
Davide Gori ◽  
Lucia Ghizzoni
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Negative Impact ◽  
Reproductive Potential ◽  
Central Precocious Puberty ◽  
Long Term Effects ◽  
Mineral Density ◽  
Long Term Outcomes ◽  
Gnrh Analogues

GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

scholarly journals Mutations of the KISS1 Gene in Disorders of Puberty

2010 ◽  
Vol 95 (5) ◽  
pp. 2276-2280 ◽  
Author(s):  
L. G. Silveira ◽  
S. D. Noel ◽  
A. P. Silveira-Neto ◽  
A. P. Abreu ◽  
V. N. Brito ◽  
...  
Keyword(s):  
Human Serum ◽  
Precocious Puberty ◽  
Inositol Phosphate ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Central Precocious Puberty ◽  
Control Group ◽  
Missense Mutations ◽  
Wild Type

Abstract Context: Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Objective: Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Patients: Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. Methods: The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Results: Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Conclusion: Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype.

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate

2018 ◽  
Vol 31 (6) ◽  
pp. 655-663 ◽  
Author(s):  
Karen O. Klein ◽  
Sanja Dragnic ◽  
Ahmed M. Soliman ◽  
Peter Bacher
Keyword(s):  
Growth Rate ◽  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
The Body ◽  
Bone Maturation ◽  
Maturation Rate ◽  
Parental Height ◽  
The Mean

Abstract Background: Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. Results: Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β−0.098 and −0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. Conclusions: Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

scholarly journals Importance of individualizing treatment decisions in girls with central precocious puberty when initiating treatment after age 7 years or continuing beyond a chronological age of 10 years or a bone age of 12 years

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marcela Vargas Trujillo ◽  
Sanja Dragnic ◽  
Petra Aldridge ◽  
Karen O. Klein
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Treatment Initiation ◽  
Central Precocious Puberty ◽  
Optimal Growth ◽  
Bone Age ◽  
Chronological Age ◽  
Gonadotropin Releasing Hormone Agonist ◽  
End Of Treatment ◽  
Treatment Plans

Abstract Objectives Gonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years. Methods Forty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA <7 vs. ≥7 years, and BA ≥12 vs. BA <12 years. Results Mean baseline CA was 6.8 years, BA, 10.2 years; and PAH, 156.4 cm. BA/CA ratio decreased from pretreatment values, averaging 1.5 to 1.2 at the end of treatment. Proportion of girls with >5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years. Conclusions PAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone.

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